Physiological changes in neurodegeneration — mechanistic insights and clinical utility

• Published in: Nature reviews. Neurology Vol. 14; no. 5; pp. 259 - 271
• Main Authors: Ahmed, Rebekah M., Ke, Yazi D., Vucic, Steve, Ittner, Lars M., Seeley, William, Hodges, John R., Piguet, Olivier, Halliday, Glenda, Kiernan, Matthew C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2018; Nature Publishing Group
• Subjects: 631/378/1385/519; 631/443/319; 692/617/375/365; Alzheimer's disease; Development and progression; Frontotemporal dementia; Medical research; Medicine & Public Health; Nervous system; Neurodegeneration; Neurology; Pathological physiology; Physiology; review-article
• ISSN: 1759-4758; 1759-4766
• DOI: 10.1038/nrneurol.2018.23

Key Points The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological systems Key changes in eating and metabolism, autonomic function, sleep and motor function have been demonstrated across several neurodegenerative conditions Key neural structures that mediate physiological change across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system Evidence from human and animal studies suggests that these changes can arise presymptomatically and worsen with disease progression, offering a potential avenue for developing biomarkers to track disease progression Further research is required to determine whether physiological changes simply result from the neurodegeneration process or also modify the neurodegenerative process, thereby providing a novel therapeutic target In this Review, Ahmed et al. look at the changes in physiological function that occur in neurodegenerative syndromes, consider the similarities and differences in these changes across conditions, and discuss the clinical utility of detecting these changes. The effects of neurodegenerative syndromes extend beyond cognitive function to involve key physiological processes, including eating and metabolism, autonomic nervous system function, sleep, and motor function. Changes in these physiological processes are present in several conditions, including frontotemporal dementia, amyotrophic lateral sclerosis, Alzheimer disease and the parkinsonian plus conditions. Key neural structures that mediate physiological changes across these conditions include neuroendocrine and hypothalamic pathways, reward pathways, motor systems and the autonomic nervous system. In this Review, we highlight the key changes in physiological processing in neurodegenerative syndromes and the similarities in these changes between different progressive neurodegenerative brain conditions. The changes and similarities between disorders might provide novel insights into the human neural correlates of physiological functioning. Given the evidence that physiological changes can arise early in the neurodegenerative process, these changes could provide biomarkers to aid in the early diagnosis of neurodegenerative diseases and in treatment trials.